Examining Region- and Cell-Type Specific Distribution of SHANK Family Genes Across Mouse and Marmoset Models using Brain Atlases and RNA-FISH Techniques

Abstract

Autism spectrum disorders (ASDs) are heterogeneous disorders that are associated with social, affective, cognitive and motor abnormalities. Phelan-McDermid Syndrome, a neurodevelopmental disorder that is accompanied by autistic behavioral phenotypes, has been shown to develop with Shank3 heterozygous deletion in humans. Comparing mouse and marmoset models of a highly penetrant risk gene such as Shank3 using RNA-FISH will lead to a better understanding of the differences between primate and non-primate animal models for studying autism and its behavioral phenotypes. In this project, census data from mice and marmosets across different regions and cell types will be analyzed to understand differences in the expression of Shank2 and Shank3 between cell types and regions. Then, RNA-FISH experiments will be run based on the cell types and regions identified from the census data. Identifying these differences in expression could inform on developing better ASD models and potentially inform gene-targeted approaches in the future. I will analyze key brain structures implicated in autism, such as neocortex, striatum and thalamus, comparing regions and cell types specific expressions between mice and marmosets.